Upon fertilization, the mammalian embryo must switch from dependence on maternal transcripts to transcribing its own genome, and in mice this involves the transient up-regulation of MERVL transposons and MERVL-driven genes at the two-cell stage. The mechanisms and requirement for MERVL and two-cell (2C) gene up-regulation are poorly understood. Moreover, this MERVL-driven transcriptional program must be rapidly shut off to allow two-cell exit and developmental progression. Here, we report that robust ribosomal RNA (rRNA) synthesis and nucleolar maturation are essential for exit from the 2C state. 2C-like cells and two-cell embryos show similar immature nucleoli with altered structure and reduced rRNA output. We reveal that nucleolar disruption via blocking RNA polymerase I activity or preventing nucleolar phase separation enhances conversion to a 2C-like state in embryonic stem cells (ESCs) by detachment of the MERVL activator Dux from the nucleolar surface. In embryos, nucleolar disruption prevents proper nucleolar maturation and Dux silencing and leads to two- to four-cell arrest. Our findings reveal an intriguing link between rRNA synthesis, nucleolar maturation, and gene repression during early development.

中文翻译：

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基于核仁的 Dux 抑制对于胚胎两细胞阶段的退出至关重要

受精后，哺乳动物胚胎必须从依赖母体转录物转变为转录自己的基因组，在小鼠中，这涉及到 MERVL 转座子和 MERVL 驱动基因在两细胞阶段的瞬时上调。对 MERVL 和双细胞 (2C) 基因上调的机制和要求知之甚少。此外，必须迅速关闭这个由 MERVL 驱动的转录程序，以允许双细胞退出和发育进程。在这里，我们报告稳健的核糖体 RNA (rRNA) 合成和核仁成熟对于退出 2C 状态至关重要。2C 样细胞和双细胞胚胎显示出相似的未成熟核仁，其结构改变，rRNA 输出减少。Dux来自核仁表面。在胚胎中，核仁破坏会阻止适当的核仁成熟和Dux沉默，并导致 2 到 4 个细胞停滞。我们的研究结果揭示了早期发育过程中 rRNA 合成、核仁成熟和基因抑制之间的有趣联系。